热休克蛋白90阻止剂增强热诱导骨肉瘤细胞杀伤的研究  

Study on HSP90 inhibitor of potentiating heat-induced cell killing osteosarcoma cells

作　　者：苟永胜[1] 裘秀春[1] 杨彤涛[1] 马保安[1] 周勇[1] 张明华[1] 周本根[1] 李伟[1] 何立宏[1] 范清宇[1] 

机构地区：[1]第四军医大学唐都医院全军骨肿瘤研究所,陕西西安710038

出　　处：《中华肿瘤防治杂志》2007年第14期1077-1080,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国科重点项目(NO.30330610);国科全面上项目(NO.3047988);中国博士后基金资助(NO.2005038259)

摘　　要：目的:探讨热休克蛋白90(heat shock protain 90,HSP90)分子伴侣复合物阻止剂17-丙烯胺基-17去甲氧基格尔德霉素(17-allyl-amide-17-demethoxgeldanamycin,17-AAG),对热诱导的骨肉瘤SOSP-9607细胞杀伤作用的影响。方法:采用干细胞集落形成实验、流式细胞术(flow cytometry,FCM)和吖啶橙荧光染色等方法观察比较单纯热疗组与热疗联合17-AAG治疗组对骨肉瘤SOSP-9607细胞活力、凋亡率及形态学影响。结果:干细胞集落形成实验显示,热疗联合17-AAG治疗组较单独热疗对骨肉瘤SOSP-9607细胞的杀伤效应明显增强,P=0.036;Annexin V-FITC染色流式细胞术结果显示,热疗联合17-AAG治疗组所致凋亡率(52.2%)大于单纯热疗组(17.5%);用吖啶橙荧光染色法观察到热疗联合17-AAG治疗组明显见骨肉瘤SOSP-9607细胞固缩着色不均而且较深,细胞核浓缩、裂解等凋亡特征。结论:HSP90分子伴侣复合物阻止剂17-AAG能增强热诱导的骨肉瘤SOSP-9607细胞的杀伤作用。OBJECTIVE： To examine the capability of a heat shock protein 90（HSP90） chaperone complex inhibitor, 17-allylamide-17-demethoxgeldanamycin（ 17AAG）, on heat-induced cell killing of osteosarcoma SOSP-9607 cells. METHODS： Osteosarcoma SOSP-9607 cells were incubated with 17AAG during heat treatment. The surviving fractions were determined by the clonogenic assay; the rates of apoptosis were analyzed by flow cytometry （FCM）. At the same time, morphologic changes of SOSP-9607 cells were observed by acridine orange staining in these groups of different treatments. RESULTS：The clonogenic assays showed that 17AAG in combination with heat synergistically potentiated heat-induced cell killing, P=0. 036. Annexin V-FITC staining revealed that the percentages of apoptotic cells were 52.2% and 17.5% in the group of combination of heat with 17AAG and the group of heat alone, respectively. Similiarly, cell shrinkage and nuclear condensation in the group of combination of heat with 17AAG were observered by acridine orange staining. CONCLUSION： The HSP90 chaperone complex inhibitor （17AAG） potentiates heat-induced cell killing of osteosarcoma SOSP-9607 cells.

关 键 词：热休克蛋白质类/代谢 骨肉瘤/病理学 骨肿瘤/病理学 细胞凋亡 

分 类 号：R738.1[医药卫生—肿瘤]